Ex Parte 7413749 et al

Patent Trial and Appeal Board

Sep 24, 2013

90010576 (P.T.A.B. Sep. 24, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
90/010,576 07/07/2009 7413749 6092-22 5412
111303 7590 09/25/2013
Ostrolenk Faber LLP
1180 Avenue of the Americas
New York, NY 10036
EXAMINER
JONES, DWAYNE C
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
09/25/2013 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte PURDUE PHARMA L.P.
Patent Owner and Appellant
____________

Appeal 2012-012211
Reexamination Control 90/010,576
Patent U.S. 7,413,749 B2
Technology Center 3900
____________

Before RICHARD M. LEBOVITZ, JEFFREY B. ROBERTSON, and
RAE LYNN P. GUEST, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
Patent Owner, Purdue Pharma L.P., appeals from the Patent
Examiner’s rejections of claims 1-40 in the above-identified ex parte
reexamination proceeding. The Board’s jurisdiction for this appeal is under
35 U.S.C. §§ 6(b), 134(b), and 306. We reverse.

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I. STATEMENT OF CASE
This appeal involves US 7,413,749 B2 (“the ‘749 patent”) which
issued August 19, 2008. A Replacement Request for Ex Parte
Reexamination of the ‘749 patent was submitted by a third-party requester
on July 7, 2009. Reexamination of the ‘749 patent was subsequently
ordered (Order Granting Request for Reexamination, Aug. 18, 2009).
The real party in interest in this ex parte reexamination proceeding is
the Patent Owner, Purdue Pharma L.P. (Appeal Br. 2, filed January 24,
2011).
The claims in the ‘749 patent are directed to dosing regimens for
administering controlled release tramadol to patients. Tramadol is “a
centrally acting synthetic opioid analgesic that is effective for the
management of moderate to severe pain.” (‘749 patent, col. 1, ll. 30-31.)
According to the patent at column 1, lines 54-60:
[T]here exists a need for a dosage regimen for a controlled
release tramadol which significantly reduces the occurrence of
and concomitant severity of adverse tramadol elicited side
effects, and thus, reduces potential discontinuation by patients
due to these effects and increases the number of patients who
may successfully treated.

II. REJECTION
Claims 1-40 are pending. Claims 1-8 were originally issued in the
‘749 patent. Claims 9-40 were added during this reexamination proceeding.
Patent Owner appeals the Examiner’s decision to reject all the pending
claims. Claims 1-40 stand rejected by the Examiner under 35 U.S.C. § 103
as obvious in view of the BW HealthWire article titled “Biovail Reports
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Second Positive Phase III Clinical Study Result for Tramadol Extended
Release Formulation,” dated January 14, 2002 (“BW HealthWire”) as
evidenced by Tramadol (PubMed Health) (“Tramadol Online”) (Appeal Br.
5: 1-4).

III. REPRESENTATIVE CLAIM
Claim 1 is representative and reads as follows:
A dosage regimen for administering tramadol to a patient
comprising administering: about 75 mg to about 125 mg of
tramadol in a controlled release dosage form once-a-day for
about 4 to about 10 days;
then about 175 mg to about 225 mg of tramadol in a
controlled release dosage form once-a-day for about 4 to about
10 days;
then about 275 mg to about 325 mg of tramadol in a
controlled release dosage form once-a-day for at least 1 day and
optionally thereafter.

IV. TEACHINGS FROM BW HEALTHWIRE
B1. “Tramadol is currently dosed 3 to 4 times per day and is
prescribed for the treatment of moderate to moderately severe pain.” (Page
1.)
B2. BW HealthWire describes the clinical results of a 12-week
randomized double-blind study in which an extended release (“ER”)
formulation of tramadol was administered once a day (“QD”). Patients
received doses of either 200 or 300 mg tramadol, or placebo. ER tramadol
300 mg was reported to be more effective than either the placebo or the 200
mg dose. (Page 1.)
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B3. “The study included an open label run-in phase to identify
patients for continuation in the double-blind phase who tolerated tramadol
and perceived a benefit.” (Page 2.)
B4.
During the 3-week run-in period, patients initiated on 100 mg
QD and maintained on their dose for at least 3 days. On Day 4,
and for the remainder of the first week, patients were permitted
to have their dose increased to 200 mg QD based upon the
tolerability of side effects. Beginning the second week, patients
were maintained on a minimum of 200 mg QD and the dose
titrated upward to 300 mg QD based upon the tolerability of
side effects. Beginning the third week, patients were escalated
to a dose of 300 mg QD and maintained at that dose for 1 week.
No further dose adjustments were permitted during the
remainder of the run-in period. Patients with pain unresponsive
to appropriate dosage adjustments or with unacceptable side
effects were dropped from the study. Eligible patients receiving
Tramadol ER 300 mg at the end of the 3-week run-in period
entered the 12-week double-blind randomized phase of the
study.
(Page 2.)
IV. DISCUSSION
The claims are directed to a “dosing regimen for administering
tramadol to a patient comprising administering” tramadol to a patient in
controlled release dosage form in specifically recited ranges of amounts
(e.g., “about 75 mg to about 125 mg”) for specifically recited time periods
(e.g., “for about 4 to about 10 days”). Independent claim 1 is representative
and reproduced in Section III above. Independent claims 9, 17, 25, and 33
are similar to claim 1, but recite narrower ranges of dosage amounts and
time periods over which the tramadol is administered.
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The Examiner found that the run-in study described in BW
HealthWire “teaches titrating tramadol ER (extended release) with ranges of
days (a dosage regimen) that overlap or lie inside the claimed daily dosage
regimen. Thus, a prima facie case of obviousness exists.” (Answer 6.)
Patent Owner did not challenge the Examiner’s determination that
amounts of tramadol administered in the run-in study overlapped with the
claimed tramadol dosages and time periods during which the tramadol is
administered. Rather, Patent Owner argued that the “run-in phase”is not a
teaching of a dosing regimen (Appeal Br. 5). Patent Owner contends that
there is no teaching that the dosage amounts or time periods utilized in the
run-in phase provided benefits to the patients (id.) Instead, Patent Owner
contends that the amounts and time periods used in the run-in study were for
selecting patients for a clinical study (id.) The purpose of the run-in phase,
according to Patent Owner, was “to preselect clinical study subjects who are
likely to have a favorable and intended response to the drug being tested.”
(Reply Br. 3).
It is well-established that, when there is a range disclosed in the prior
art, and the claimed invention overlaps or falls within that range, there is a
presumption of obviousness. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir.
2003); Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed.
Cir. 2004). The reason for this presumption, as explained in Peterson, is that
the “normal desire of scientists or artisans to improve upon what is already
generally known provides the motivation to determine where in a disclosed
set of percentage ranges is the optimum combination of percentages.”
Peterson, 315 F.3d at 330. Thus, while there is a presumption of
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obviousness when a claimed range overlaps or falls within a prior art range,
there still must be a reason to optimize the prior art range to have arrived at
the claimed range. Accordingly, the issue in this rejection is whether the
skilled worker would have had a reason to optimize the values in the run-in
phase to have arrived at the values recited in the claims.
The Examiner gave the following reasons to optimize the values
taught in the run-in study:
[I]t would have been obvious to one having ordinary skill in the
art to select the claimed ranges for the dosage regimen (dosage
amounts and administration periods) of controlled-release
tramadol as taught by BW Health Wire in order to arrive at the
claimed invention with a reasonable expectation of success in
formulating a dosing regimen of tramadol that provides
continued analgesic relief of a patient while minimizing
unwanted and/or adverse side effects to the patient. In addition,
the skilled artisan would have been motivated to modify and
optimize the dosing regimen of BW HealthWire to provide
improve patient care and comfort.
(Answer 7.)
It is true, as the Examiner found, that the claimed dosing regimen was
designed to provide “continued analgesic relief of a patient while
minimizing unwanted and/or adverse side effects to the patient.” (Id.) The
claimed dosing regimen is described in the ‘749 patent as “increas[ing] the
therapeutic benefit of controlled release tramadol by minimizing adverse
effects.” (‘749 patent, col. 1, ll. 22-24.) The patent teaches that
“[c]ontrolled release tramadol hydrochloride formulations were developed
for the relief of mild to moderate pain by administration once a day, to
reduce the frequency of dosing.” (Id. at col. 13, ll. 27-29.) Thus, while the
claims do not expressly recite that the dosing regimen is effective to treat
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pain and minimize adverse effects, one of ordinary skill in the art would
have understood, upon reading the ‘749 patent’s written description, that the
claimed dosages and time periods over which the dosages are administered
achieve such a result.
On the other hand, the purpose of the run-in study described in BW
HealthWire was not to treat pain. As pointed out by Patent Owner, the
“open label run-in phase” study was performed “to identify patients for
continuation in the double-blind phase who tolerated tramadol and perceived
a benefit.” (B3.) There is no disclosure in BW HealthWire that the dosage
was titrated or escalated in the run-in study to achieve greater therapeutic
efficacy in treating pain. Rather, BW HealthWire reports that the dosages in
the run-in study were titrated upward “based upon the tolerability of side
effects.” (B4.) In other words, dosages were increased to identify those
subjects who would experience side effects in order to eliminate them from
the subsequent 12-week study (B2). When tramadol was administered in the
12-week study to determine efficacy, i.e., to treat pain, the dosages were
constant through the 12-week period, at either 200mg or 300mg. (B2.)
The Examiner’s reasoning that the skilled worker would have
modified the values in the run-in study to provide “continued analgesic
relief” and “improve[d] patient care” is not consistent with the disclosure in
BW HealthWire that dosages in the run-in study were adjusted only on the
basis of side effects. The only disclosure about analgesic relief related to the
run-in study is that “[p]atients with pain unresponsive to appropriate dosage
adjustments . . . were dropped from the study.” ( B4.) Thus, we find the
Examiner’s reasoning erroneous. The Examiner did not provide adequate
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reason that optimizing on the basis of tolerability of side effects would have
lead to the ranges recited in the claims which were selected to achieve
therapeutic benefit while minimizing adverse effects.
In sum, the run-in study described in BW HealthWire was designed to
eliminate subjects from the longer term 12-week study who were not
responsive to tramadol or who experienced unacceptable side effects. Thus,
we do not see a reason to have optimized the dosages to achieve better
therapeutic effect, as found by the Examiner, since that was not the purpose
of the run-in study.

REVERSED

PATENT OWNER:

OSTROLENK FABER LLP
1180 AVENUE OF THE AMERICAS
NEW YORK, NY 10036